Expedition 5300: limits of human adaptations in the highest city in the world.

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000-5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude-related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 ± 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 ± 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO2  = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues.

Diagnostic work-up of exercise-induced laryngeal obstruction.

PURPOSE: Exercise-induced laryngeal obstruction (EILO) is suspected when dyspnea associated with upper airway symptoms is triggered by exercise. This condition affects mainly adolescent athletes. Visualization of the obstruction, while the patient is experiencing the symptoms during continuous laryngoscopy during exercise (CLE-test) is the gold standard for diagnosing EILO. Our study aims to evaluate the prevalence of EILO in a population presenting exercise-induced inspiratory symptoms (EIIS) or uncontrolled asthma with exertional symptoms. The second objective was to evaluate the diagnostic strength of laryngology consultation (LC) and pulmonary function tests (PFTs). METHODS: All patients referred to our center for EIIS or uncontrolled asthma with exertional symptoms were included. EILO diagnosis was made if Maat score was > 2 for patients with CLE-test or if there were inspiratory anomalies on PFTs and LC. The sensitivity and specificity of LC and PFTs as diagnostic tools were calculated considering CLE-test as the gold standard. RESULTS: Sixty two patients were referred to our center for EIIS or uncontrolled asthma with exertional symptoms. EILO was diagnosed in 28 patients (56%) with associated asthma in 9 patients (18%). The sensibility and specificity of LC for supraglottic anomalies were 75% and 60%, respectively. The sensibility and specificity of PFTs were 61% and 89%, respectively. CONCLUSIONS: There was a high prevalence of EILO among patients with EIIS and uncontrolled asthma. Some clinical characteristics might guide the diagnosis. Nevertheless, CLE-test remained the gold standard for EILO diagnosis and identification of the dysfunctional upper airway site to provide specific management.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Hypoxic high-intensity interval training in individuals with overweight and obesity.

Combining moderate-intensity exercise training with hypoxic exposure may induce larger improvement in cardiometabolic risk factors and health status compared with normoxic exercise training in obesity. Considering the greater cardiometabolic effects of high-intensity intermittent training (HIIT), we hypothesized that hypoxic high-volume HIIT (H-HIIT) would induce greater improvement in cardiorespiratory fitness and health status despite a lower absolute training workload than normoxic HIIT (N-HIIT) in overweight/obesity. Thirty-one subjects were randomized to an 8-week H-HIIT [10 male and 6 female; age: 51.0 ± 8.3 years; body mass index (BMI): 31.5 ± 4 kg·m-2] or N-HIIT (13 male and 2 female; age: 52.0 ± 7.5 years; BMI: 32.4 ± 4.8 kg·m-2) program (3 sessions/week; cycling at 80% or 100% of maximal workload for H-HIIT and N-HIIT, respectively; target arterial oxygen saturation for H-HIIT 80%, [Formula: see text] ∼0.12, i.e., ∼4,200 meters above sea level). Before and after training, the following evaluations were performed: incremental maximal and submaximal cycling tests, pulse-wave velocity, endothelial function, fasting glucose, insulin, lipid profile, and body composition. Maximal exercise (V̇o2peak: H-HIIT +14.2% ± 8.3% vs. N-HIIT +12.1 ± 8.8%) and submaximal (ventilatory thresholds) capacity and exercise metabolic responses (power output at the crossover point and at maximal fat oxidation rate) increased significantly in both groups, with no significant difference between groups and without other cardiometabolic changes. H-HIIT induced a greater peak ventilatory response (ANOVA group × time interaction F = 7.4, P = 0.016) compared with N-HIIT. In overweight/obesity, the combination of normobaric hypoxia and HIIT was not superior for improving cardiorespiratory fitness improvement compared with HIIT in normoxia, although HIIT in hypoxia was performed at a lower absolute training workload.

Changes in cardiac function following a speed ascent to the top of Europe at 4808 m.

PURPOSE: Both prolonged exercise and acute high-altitude exposure are known to induce cardiac changes. We sought to describe the cardiac responses to speed climbing at high-altitude, including left ventricular (LV) performance assessment using the myocardial work index (MWI), a new index derived from 2D speckle tracking echocardiography (STE). METHODS: Eleven elite alpinists (9 males, age: 26 ± 4 years) were evaluated before and immediately after a speed ascent of the Mont-Blanc (4808 m) by echocardiography using conventional measurements as well as STE and MWI computation with derivate parameters as global work efficiency (GWE) or global wasted work (GWW). RESULTS: Athletes performed a long-duration (8 h 58 min ± 60 min) and intense (78 ± 4% of maximal heart rate) ascent under gradual hypoxic conditions (minimal SpO2 at 4808 m: 71 ± 4%). Hypoxic exercise-induced cardiac fatigue was observed post-ascent with a change in right ventricular (RV) and LV systolic function (RV fractional area change: - 20 ± 23%, p = 0.01; LV global longitudinal strain change: - 8 ± 9%, p = 0.02), as well as LV geometry and RV-LV interaction alterations with emergence of a D-shape septum in 5/11 (46%) participants associated with RV pressure overload (mean pulmonary arterial pressure change: + 55 ± 20%, p < 0.001). Both MWI and GWE were reduced post-ascent (- 21 ± 16%, p = 0.004 and - 4 ± 4%, p = 0.007, respectively). Relative decrease in MWI and GWE were inversely correlated with increase in GWW (r = - 0.86, p = 0.003 and r = -0.97, p < 0.001, respectively). CONCLUSIONS: Prolonged high-altitude speed climbing in elite climbers is associated with RV and LV function changes with a major interaction alteration. MWI, assessing the myocardial performance, could be a new tool for evaluating LV exercise-induced cardiac fatigue.

Effect of a speed ascent to the top of Europe on cognitive function in elite climbers.

PURPOSE: The combined effects of acute hypoxia and exercise on cognition remain to be clarified. We investigated the effect of speed climbing to high altitude on reactivity and inhibitory control in elite climbers. METHODS: Eleven elite climbers performed a speed ascent of the Mont-Blanc (4810 m) and were evaluated pre- (at 1000 m) and immediately post-ascent (at 3835 m). In both conditions, a Simon task was done at rest (single-task session, ST) and during a low-intensity exercise (dual-task session, DT). Prefrontal cortex (PFC) oxygenation and middle cerebral artery velocity (MCAv) were monitored using near-infrared spectroscopy and transcranial Doppler, respectively, during the cognitive task. Self-perceived mental fatigue and difficulty to perform the cognitive tests were estimated using a visual analog scale. Heart rate and pulse oxygenation (SpO2) were monitored during the speed ascent. RESULTS: Elite climbers performed an intense (~ 50% of the time ≥ 80% of maximal heart rate) and prolonged (8h58 ± 6 min) exercise in hypoxia (minimal SpO2 at 4810 m: 78 ± 4%). Reaction time and accuracy during the Simon task were similar pre- and post-ascent (374 ± 28 ms vs. 385 ± 39 ms and 6 ± 4% vs. 5 ± 4%, respectively; p > 0.05), despite a reported higher mental fatigue and difficulty to perform the Simon task post-ascent (all p < 0.05). The magnitude of the Simon effect was unaltered (p > 0.05), suggesting a preserved cognitive control post-ascent. Pattern of PFC oxygenation and MCAv differed between pre- and post-ascent as well as between ST and DT conditions. CONCLUSIONS: Cognitive control is not altered in elite climbers after a speed ascent to high-altitude despite substantial cerebral deoxygenation and fatigue perception.

High-intensity interval training to promote cerebral oxygenation and affective valence during exercise in individuals with obesity.

Left/right prefrontal cortex (PFC) activation is linked to positive/negative affects, respectively. Besides, larger left PFC oxygenation during exercise relates to higher cardiorespiratory fitness (CRF). High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. The influence of training on PFC oxygenation and affects during exercise in individuals with obesity is, however, currently unknown. Twenty participants with obesity (14 males, 48 ± 8 years, body-mass index = 35 ± 6 kg·m-2) were randomised to MICT [50% peak work rate (WRpeak)] or HIIT (1-min bouts 100% WRpeak; 3 sessions/week, 8 weeks). Before/after training, participants completed an incremental ergocycle test. Near-infrared spectroscopy and the Feeling Scale assessed PFC oxygenation and affects during exercise, respectively. Improvements in CRF (e.g., WRpeak: 32 ± 14 vs 20 ± 13 W) were greater after HIIT vs MICT (p < 0.05). Only HIIT induced larger left PFC oxygenation (haemoglobin difference from 7 ± 6 to 10 ± 7 µmol) and enhanced affective valence (from 0.7 ± 2.9 to 2.2 ± 2.0; p < 0.05) at intensities ≥ second ventilatory threshold. Exercise-training induced changes in left PFC oxygenation correlated with changes in CRF [e.g., WRpeak (% predicted), r = 0.46] and post-training affective valence (r = 0.45; p < 0.05). HIIT specifically improved left PFC oxygenation and affects during exercise in individuals with obesity. Implementing HIIT in exercise programmes may therefore have relevant implications for the management of obesity, since greater affective response to exercise is thought to be associated with future commitment to physical activity.

Effects of high intensity interval training on sustained reduction in cardiometabolic risk associated with overweight/obesity. A randomized trial.

Background: Considering the potential greater cardiocirculatory effects of high intensity interval training (HIIT), we hypothesized that a 2-month supervised high volume short interval HIIT would induce greater improvements in CRF and cardiometabolic risk and increase long-term maintenance to physical activity compared to isocaloric moderate intensity continuous training (MICT) in overweight/obesity. Methods: Sixty (19 females) subjects with overweight/obesity were randomized to three training programs (3 times/week for 2 months): MICT (45 min, 50% peak power output-PPO), HIIT (22 × 1-min cycling at 100% PPO/1-min passive recovery) and HIIT-RM (RM: recovery modulation, i.e. subjects adjusted passive recovery duration between 30s and 2 min). After the intervention, participants no longer benefited from supervised physical activity and were instructed to maintain the same exercise modalities on their own. We assessed anthropometrics, body composition, CRF, fat oxidation, lipid profile, glycemic balance, low-grade inflammation, vascular function, spontaneous physical activity and motivation for eating at three time points: baseline (T0), 4 days after the end of the 2-month supervised training program (T2) and 4 months after the end of the training program (T6). Results: HIIT/HIIT-RM induced greater improvement in VO2peak (between +14% and +17%), power output at ventilatory thresholds and at maximal fat oxidation rate (+25%) and waist circumference (-1.53 cm) compared to MICT and tended to decrease insulin resistance. During the four-month follow-up period during which exercise in autonomy was prescribed, HIIT induced a greater preservation of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL. Conclusion: We have shown greater short-term benefits induced by a high volume short interval (1 min) HIIT on cardiorespiratory fitness and cardiometabolic risk over an isocaloric moderate intensity continuous exercise in persons with overweight/obesity. We also showed greater long-term effects (i.e. after 4 months) of this exercise modality on the maintenance of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL.

Blood viscosity and its determinants in the highest city in the world.

KEY POINTS: Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate-to-severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit. ABSTRACT: Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety-three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate-to-severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s-1 : 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate-to-severe CMS (at 45 s-1 : 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.

Cardiovascular and metabolic responses to passive hypoxic conditioning in overweight and mildly obese individuals.

Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.3 yr, 31.7 ± 3.5 kg/m2) were randomized into three 8-wk interventions (three 1-h sessions per week): sustained hypoxia (SH), arterial oxygen saturation ([Formula: see text]) = 75%; IH, 5 min [Formula: see text] = 75% - 3 min normoxia; normoxia. Ventilation, heart rate, blood pressure, and tissue oxygenation were measured during the first and last hypoxic conditioning sessions. Vascular function, blood glucose and insulin, lipid profile, nitric oxide metabolites, and oxidative stress were evaluated before and after the interventions. Both SH and IH increased ventilation in hypoxia (+1.8 ± 2.1 and +2.3 ± 3.6 L/min, respectively; P < 0.05) and reduced normoxic diastolic blood pressure (-12 ± 15 and -13 ± 10 mmHg, respectively; P < 0.05), whereas changes in normoxic systolic blood pressure were not significant (+3 ± 9 and -6 ± 13 mmHg, respectively; P > 0.05). IH only reduced heart rate variability (e.g., root-mean-square difference of successive normal R-R intervals in normoxia -21 ± 35%; P < 0.05). Both SH and IH induced no significant change in body mass index, vascular function, blood glucose, insulin and lipid profile, nitric oxide metabolites, or oxidative stress, except for an increase in superoxide dismutase activity following SH. This study indicates that passive hypoxic conditioning in obese individuals induces some positive cardiovascular and respiratory improvements despite no change in anthropometric data and even a reduction in heart rate variability during IH exposure.

A short bout of high-intensity intermittent exercise before moderate-intensity prolonged exercise as a mean to potentiate fat oxidation ?

Moderate-intensity continuous exercise (MICE) improves fat oxidation. High-intensity intermittent exercise (HIIE) is thought to have a greater potential for fat oxidation but it might be too demanding in the long term for patients. We hypothesized that an initial bout of HIIE could maximize fat oxidation during MICE and the following passive recovery. Eighteen healthy participants performed two acute isocaloric exercise sessions at random. MICE consisted of 45-min cycling at 50% of maximal aerobic power (Pmax). COMB began with five 1-min bouts of HIIE at Pmax (interspaced with 1-min recovery periods) followed by 35-min MICE. Gas exchange allowed substrate oxidation rate assessment.Expressed as a % of energy expenditure, fat oxidation (%) increased during in the passive recovery following COMB (Recovery: 36.0 ± 19.4 vs 23.0 ± 20.3%; ES: 0.66; p < 0.0001). An initial bout of HIIE preceding a prolonged moderate-intensity exercise may potentiate fat oxidation during the following recovery. This might be relevant for health management of overweight/obese persons.

Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men.

NEW FINDINGS: What is the central question of this study? What is the effect of acute NO precursor intake on vascular function, muscle and cerebral oxygenation and peripheral and central neuromuscular fatigue during knee-extension exercise? What is the main finding and its importance? Acute NO precursor ingestion increases the plasma concentrations of NO precursors (nitrate, arginine and citrulline) and enhances post-ischaemic vasodilatation, but has no significant effect on muscle and cerebral oxygenation, peripheral and central mechanisms of neuromuscular fatigue and, consequently, does not improve exercise performance. ABSTRACT: Nitric oxide (NO) plays an important role in matching blood flow to oxygen demand in the brain and contracting muscles during exercise. Previous studies have shown that increasing NO bioavailability can improve muscle function. The aim of this study was to assess the effect of acute NO precursor intake on muscle and cerebral oxygenation and on peripheral and central neuromuscular fatigue during exercise. In four experimental sessions, 15 healthy men performed a thigh ischaemia-reperfusion test followed by submaximal isometric knee extensions (5 s on-4 s off; 45% of maximal voluntary contraction) until task failure. In each session, subjects drank a nitrate-rich beetroot juice containing 520 mg nitrate (N), N and citrulline (6 g; N+C), N and arginine (6 g; N+A) or a placebo (PLA). Prefrontal cortex and quadriceps near-infrared spectroscopy parameters were monitored continuously. Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. The post-ischaemic increase in thigh blood total haemoglobin concentration was larger in N (10.1 ± 3.7 mmol) and N+C (10.9 ± 3.3 mmol) compared with PLA (8.2 ± 2.7 mmol; P < 0.05). Nitric oxide precursors had no significant effect on muscle and cerebral oxygenation or on peripheral and central mechanisms of neuromuscular fatigue during exercise. The total number of knee extensions did not differ between sessions (N, 71.9 ± 33.2; N+A, 73.3 ± 39.4; N+C, 74.6 ± 34.0; PLA, 71.8 ± 39.9; P > 0.05). In contrast to the post-ischaemic hyperaemic response, NO bioavailability in healthy subjects might not be the limiting factor for tissue perfusion and oxygenation during submaximal knee extensions to task failure.

Pulmonary hemodynamics responses to hypoxia and/or CO2 inhalation during moderate exercise in humans.

In this study, we hypothesized that adding CO2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O2), inhaled CO2 (4.5% CO2), and combination of hypoxia and inhaled CO2. Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO2 inhalation + 135%, combined + 184%, hypoxia + 217% (p < 0.001). CO was higher when inhaling O2-poor gas mixtures with or without CO2 (~ 17 L min-1) than in the other conditions (~ 14 L min-1, p < 0.001). Exercise induced a significant decrease in TPR in the four conditions (p < 0.05) but less marked in hypoxia (- 19% of the resting value in ambient air) than in ambient (- 33%) and in both CO2 inhalation and combined condition (- 29%). We conclude that (1) acute CO2 inhalation did not significantly modify pulmonary hemodynamics during moderate exercise. (2) CO2 adjunction to hypoxic gas mixture did not modify CO, despite a higher CaO2 in combined condition than in hypoxia. (3) TPR was lower in combined than in hypoxia condition, limiting sPAP increase in combined condition.

Maximal exercise capacity in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis.

Maximal aerobic capacity is a strong health predictor and peak oxygen consumption (V'O2peak) is considered a reflection of total body health. No systematic reviews or meta-analyses to date have synthesised the existing data regarding V'O2peak in patients with obstructive sleep apnoea (OSA).A systematic review of English and French articles using PubMed/MEDLINE and Embase included studies assessing V'O2peak in OSA patients either in mL·kg-1·min-1 compared with controls or in % predicted. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence.Mean V'O2peak expressed in mL·kg-1·min-1 was significantly lower in patients with OSA than in controls (mean difference -2.7 mL·kg-1·min-1; p<0.001; n=850). This reduction in V'O2peak was found to be larger in non-obese patients (body mass index <30 kg·m-2). Mean V'O2peak % pred was 89.9% in OSA patients (n=643).OSA patients have reduced maximal aerobic capacity, which can be associated with increased cardiovascular risks and reduced survival in certain patient subgroups. Maximal exercise testing can be useful to characterise functional limitation and to evaluate health status in OSA patients.

Effect of ageing on hypoxic exercise cardiorespiratory, muscle and cerebral oxygenation responses in healthy humans.

NEW FINDINGS: What is the central question of this study? This study aimed to determine the effect of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia during maximal incremental exercise. What is the main finding and its importance? Older healthy subjects had preserved hypoxic cardiorespiratory and tissue oxygenation responses at rest and during moderate exercise. At maximal exercise, they had a reduced hypoxic ventilatory response but similar maximal power output reduction compared with young individuals. This study suggests that until moderate exercise, hypoxic responses are preserved until the age of 70 years and therefore that ageing is not a contraindication for high-altitude sojourn. This study assessed the effects of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia both at rest and during incremental maximal exercise. Sixteen young (20-30 years old) and 15 older healthy subjects (60-70 years old) performed two maximal incremental cycling tests in normoxia and hypoxia (inspiratory oxygen fraction 12%). Cardiorespiratory responses, prefrontal cortex and quadriceps tissue oxygenation (near-infrared spectroscopy) were measured during exercise as well as during hypercapnia at rest. The hypoxic ventilatory response was similar in young compared with older individuals at rest and during moderate-intensity exercise (50% maximal power output: young 0.9 ± 0.2 versus older 1.1 ± 0.8 l min-1  %-1 ; P > 0.05) but larger in young subjects during high-intensity exercise (maximal power output: 2.2 ± 0.8 versus 1.8 ± 1.1 l min-1  %-1 ; P < 0.05). The hypoxic cardiac response did not differ between groups both at rest and during exercise. During exercise in hypoxia, young subjects showed greater deoxygenation than older subjects, at both the prefrontal cortex and quadriceps levels. The hypoxia-induced reduction in maximal power output (young -32 ± 5% versus older -30 ± 6%; P > 0.05) and the hypercapnic responses did not differ between groups. Older healthy and active individuals below the age of 70 years have cardiorespiratory and tissue oxygenation responses to hypoxia similar to young individuals both at rest and during moderate-intensity exercise. Despite a lower hypoxic ventilatory response at maximal exercise, older individuals have similar oxygen desaturation and maximal power output reduction compared with young subjects.

Recognition and significance of pathological T-wave inversions in athletes.

BACKGROUND: Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1-V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations. METHODS AND RESULTS: Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease. CONCLUSIONS: PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.

Mitochondrial function following downhill and/or uphill exercise training in rats.

INTRODUCTION: The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH-DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. METHODS: Thirty-two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH-DH. Twenty-four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. RESULTS: Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. CONCLUSIONS: Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH-trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54: 925-935, 2016.

Right Heart Hemodynamics in Pulmonary Hypertension　- An Echocardiography and Catheterization Study.

BACKGROUND: Echocardiography (ECHO) plays a key role in both the diagnosis and prognosis of pulmonary hypertension (PH). Many equations have been published to assess right heart hemodynamics using ECHO. The objective of this study was to test the accuracy and precision of different echocardiographic equations in comparison with the right heart catheterization. METHODS AND RESULTS: Complete right heart hemodynamic assessments were prospectively obtained from 115 individuals (mean age 66±1 years; 57 males) who had known or suspected PH. Several equations were tested for the estimation of right atrial pressure, mean and systolic pulmonary artery pressure (MPAP), cardiac output, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). The accuracy of ECHO was good, with a mean difference <2 mmHg for all of the pressure calculations and ±0.6 L/min for cardiac output. However, the PVR estimation was weak using any one of the formulae. For all the parameters, the precision of ECHO was moderate. The MPAP calculation detected PH with a sensibility of 97% and specificity of 83%. However, ECHO underdiagnosed post-capillary PH. CONCLUSIONS: ECHO is a good method for the diagnosis of PH, with an adequate calculation of right pressures, but cannot accurately calculate PCWP and PVR. (Circ J 2016; 80: 2019-2025).

Effect of eccentric versus concentric exercise training on mitochondrial function.

INTRODUCTION: The effect of eccentric (ECC) versus concentric (CON) training on metabolic properties in skeletal muscle is understood poorly. We determined the responses in oxidative capacity and mitochondrial H2 O2 production after eccentric (ECC) versus concentric (CON) training performed at similar mechanical power. METHODS: Forty-eight rats performed 5- or 20-day eccentric (ECC) or concentric (CON) training programs. Mitochondrial respiration, H2 O2 production, citrate synthase activity (CS), and skeletal muscle damage were assessed in gastrocnemius (GAS), soleus (SOL) and vastus intermedius (VI) muscles. RESULTS: Maximal mitochondrial respiration improved only after 20 days of concentric (CON) training in GAS and SOL. H2 O2 production increased specifically after 20 days of eccentric ECC training in VI. Skeletal muscle damage occurred transiently in VI after 5 days of ECC training. CONCLUSIONS: Twenty days of ECC versus CON training performed at similar mechanical power output do not increase skeletal muscle oxidative capacities, but it elevates mitochondrial H2 O2 production in VI, presumably linked to transient muscle damage.

Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.